This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Protection against many intracellular pathogens is provided by CD8 T cells, and pathogen-specific CD8 T cells are thought to need CD4 T cell help to develop into effective memory CD8 T cells. Since murine CD8 T cells do not transcribe MHC class II genes, several models have proposed antigen presenting cells (APCs) as intermediaries required for CD4 T cells to deliver their help to CD8 T cells. We have demonstrates the presence of MHC class II molecules on activated murine CD8 T cells in vitro as well as in vivo. These CD8 T cells acquire MHC class II from their activating APCs, particularly CD11c positive dendritic cells (DCs), via a process called trogocytosis. Transferred MHC class II molecules on activated murine CD8 T cells were functionally competent and could directly stimulate specific indicator CD4 T cells. CD8 T cells that were "helped" in vitro and subsequently allowed to rest in vivo showed enhanced recall responses upon challenge compared to "helpless" CD8 T cells;in contrast, no differences were seen upon immediate challenge. These data indicate that direct CD8:CD4 T cell interactions may significantly contribute to help for CD8 T cells. Furthermore, this mechanism may enable CD8 T cells to communicate with different subsets of interacting CD4 T cells that could modulate immune responses. These studies could have implications for HIV/AIDS research.